Tollison's first academic position as a Ph.D. was at Cornell University, where he would teach from 1969 until 1973. He then took a job at Texas A&M University where he became the economics department head after a little more than a year. He held this position with Texas A&M until 1977 when, after having spent a year as a visiting professor at the University of Miami's law school, Tollison accepted a new post at Virginia Tech as professor in that school's economics department. Tollison left Virginia Tech in 1981 to work in various roles with the Federal Trade Commission until 1983.

Tollison's areas of particular interest included the economics of religion, history of economic thought, sports economics, antitrust theory, and tobacco policy. His textbook with Robert Ekelund, Economics, is now in its seventh edition.

According to a Libertarian Forum review of Tollison and Ekelund's Mercantilism as a Rent Seeking Society, a study of the political economy of mercantilism,

...using public choice analysis, Ekelund and Tollison assert that English mercantilism declined because the rise of parliamentary power raised the lobbying costs for monopoly privileges. As parliament refused to delegate its newly won powers to anybody, any prospective monopolist had to secure majorities in the legislature as well as the acquiescence of the king.... [T]he authors stress the similarity between mercantilism and present-day economic regulation, despite the changes in the political system.[5]

Tollison's The National Collegiate Athletic Association: A Study in Cartel Behavior, in addition to a number of journal articles on the economics of sports,[6][7] led to Tollison's work being frequently cited in the area of sports economics.[8]